Raising the bar for using surrogate endpoints in drug regulation and health technology assessment

<div>In June 2021, the US Food and Drug Administration</div><div>granted accelerated approval to aducanumab for</div><div>treating Alzheimer’s disease based on the drug’s</div><div>amyloid reducing effects. This was despite evidence</div><div>from several earlier studies that shrinkage of</div><div>β-amyloid protein plaques does not predictably delay</div><div>cognitive impairment.1 The controversial decision</div><div>has drawn attention to the use of surrogate</div><div>endpoints—laboratory values, radiographic images,</div><div>or other physical measures that may serve as</div><div>indicators of clinical outcomes such as symptom</div><div>control or mortality—in clinical trials of new drugs.2</div><div>In fact, the approval of aducanumab is only the latest</div><div>example of growing regulatory reliance on surrogate</div><div>endpoints, even though their use can cause problems</div><div>for patients, clinicians, drug regulators, and health</div><div>technology assessment bodies.</div><div>We argue for more selective use of surrogate</div><div>endpoints when evaluating new drugs, restricting</div><div>their use to chronic diseases, especially when</div><div>collecting data on patient relevant clinical outcomes</div><div>requires trials with unattainably long follow up.</div>